Positron emission tomography (PET) is widely used to map the cerebral metabolic rate of glucose (CMRG) and is widely used to indicate cognitive and outcome status in the clinical arena. However, use of this imaging modality in clinically relevant small animal models of disease remains infrequent, and the majority of microPET imaging studies remain non-quantitative. Major impediments to more wide-spread use of quantitative microPET include blood sampling requirements. Solving the methodological issues that have limited the utility of small animal PET imaging for accurate and repeated quantitative measurements of CMRG will provide an important tool to enhance research in a variety of disease states. Studies are proposed to improve in vivo, multi-time-point quantification of CMRG by integrating small animal microPET with microfluidic plasma sampling technology. In vivo CMRG values determined using this automated microfluidics methodology will be compared against those determined using traditional, manually drawn sampling methods in the same animals. A second microPET study will determine the accuracy and utility of a minimally-invasive method of simultaneous measurement of blood and brain glucose isotope concentration. Since PET imaging is used so extensively in the neurosurgical clinic to monitor patients with traumatic brain injury (TBI) we will conduct a proof-of-principle study using the optimal microPET methods determined in our second microPET study to quantify the acute post-injury depression of CMRG and its recovery in an experimental model of mild-moderate unilateral TBI in rats. The accuracy and reliability of microPET-based CMRG values will be compared against values derived from end-point standard autoradiography methods. Successful completion of the proposed research will make multi-time-point, quantitative microPET imaging of small animals safe and routinely feasible. This will represent a major advance in the utility of this important translational research tool and should enhance progress in the monitoring and development of potential therapies for treatment of TBI and other diseases of the central nervous system. PUBLIC HEALTH RELEVANCE: The studies will be performed to improve the safety and reliability and to reduce the number of invasive procedures needed to conduct quantitative imaging of brain glucose utilization in small animals. A new automated plasma sampling device that is capable of taking very small samples of blood as well as separating plasma from the blood cells will be developed and integrated into current brain imaging procedures. Rates of brain glucose use will be calculated, comparing the values obtained in calculations using blood plasma samples or a single plasma sample in combination with imaging glucose uptake in both heart and brain. The optimal imaging method will be used to monitor changes in brain glucose use over time in rats with experimental traumatic brain injury. Upon completion of this project a new imaging tool will be available to researchers to study brain function under physiologically stable conditions with minimal radiation exposure.